The cognitive abilities that characterize humans are thought to emerge from unique features of the cortical circuit architecture of the human brain, which include increased cortico–cortical connectivity. However, the evolutionary origin of these changes in connectivity and how they affected cortical circuit function and behaviour are currently unknown. The human-specific gene duplication SRGAP2C emerged in the ancestral genome of the Homo lineage before the major phase of increase in brain size^1,2. SRGAP2C expression in mice increases the density of excitatory and inhibitory synapses received by layer 2/3 pyramidal neurons (PNs)^3,4,5. Here we show that the increased number of excitatory synapses received by layer 2/3 PNs induced by SRGAP2C expression originates from a specific increase in local and long-range cortico–cortical connections. Mice humanized for SRGAP2C expression in all cortical PNs displayed a shift in the fraction of layer 2/3 PNs activated by sensory stimulation and an enhanced ability to learn a cortex-dependent sensory-discrimination task. Computational modelling revealed that the increased layer 4 to layer 2/3 connectivity induced by SRGAP2C expression explains some of the key changes in sensory coding properties. These results suggest that the emergence of SRGAP2C at the birth of the Homo lineage contributed to the evolution of specific structural and functional features of cortical circuits in the human cortex.

人类特有的认知能力被认为源于人脑皮层回路结构的独特特征，其中包括增加的皮层-皮层连通性。然而，这些连接变化的进化起源以及它们如何影响皮层回路功能和行为目前尚不清楚。人类特有的基因重复SRGAP2C在大脑大小增加的主要阶段之前出现在人系的祖先基因组中^1,2。SRGAP2C 在小鼠中的表达增加了第 2/3 层锥体神经元 (PN) 接收的兴奋性和抑制性突触的密度^3,4,5. 在这里，我们表明由 SRGAP2C 表达诱导的第 2/3 层 PN 接收的兴奋性突触数量增加源于局部和远程皮质 - 皮质连接的特定增加。在所有皮层 PN 中针对 SRGAP2C 表达进行人源化的小鼠显示，由感官刺激激活的第 2/3 层 PN 的比例发生了变化，并且学习皮层依赖性感觉辨别任务的能力增强。计算模型表明，由 SRGAP2C 表达引起的第 4 层到第 2/3 层连接性的增加解释了感觉编码特性的一些关键变化。这些结果表明SRGAP2C的出现是在人属诞生时谱系有助于人类皮质中皮质回路的特定结构和功能特征的进化。